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 Table of Contents  
Year : 2012  |  Volume : 2  |  Issue : 4  |  Page : 144-147

Bevacizumab treatment for choroidal neovascularization in a patient with chorioretinopathy resembling presumed ocular histoplasmosis syndrome

Department of Ophthalmology, Chiayi Christian Hospital, Chiayi, Taiwan

Date of Web Publication7-Dec-2012

Correspondence Address:
Chong-Bin Tsai
539 Jhongsiao Road, Chiayi
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Source of Support: None, Conflict of Interest: None

DOI: 10.1016/j.tjo.2012.06.003

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Presumed ocular histoplasmosis syndrome (POHS) is rare in Taiwan. We report on a patient with a clinical picture resembling POHS who was successfully treated with intravitreal bevacizumab. A 42-year-old woman had blurred vision of her right eye. Ophthalmological examination revealed multiple juxtapapillary and peripheral punched-out chorioretinal scars. Fluorescein angiography and optic coherence tomography showed subfoveal choroidal neovascularization (CNV). She received three injections of intravitreal bevacizumab. The CNV regressed after treatment. Her visual acuity maintained 20/20 at 1 year follow-up. Taiwan is not an endemic area for histoplasmosis. Clinicians should be cautious in differential diagnosis of the clinical presentation of POHS or similar disease entities. Early identification and timely treatment with intravitreal bevacizumab may rescue the patient from vision loss.

Keywords: choroidal neovascularization, intravitreal bevacizumab, presumed ocular histoplasmosis syndrome

How to cite this article:
Tsai CB, Tan CY, Yang PM, Chang KP. Bevacizumab treatment for choroidal neovascularization in a patient with chorioretinopathy resembling presumed ocular histoplasmosis syndrome. Taiwan J Ophthalmol 2012;2:144-7

How to cite this URL:
Tsai CB, Tan CY, Yang PM, Chang KP. Bevacizumab treatment for choroidal neovascularization in a patient with chorioretinopathy resembling presumed ocular histoplasmosis syndrome. Taiwan J Ophthalmol [serial online] 2012 [cited 2022 Nov 29];2:144-7. Available from: https://www.e-tjo.org/text.asp?2012/2/4/144/203735

  1. Introduction Top

Histoplasmosis is a common endemic mycosis in United States, especially in states around the Mississippi and Ohio River Valleys.[1] The fungus is carried in birds and bats. Human systemic infections are largely asymptomatic, and ocular symptoms usually occur years after primary exposure. The ocular sequela is called presumed ocular histoplasmosis syndrome (POHS), which is characterized by peripapillary atrophic chorioretinal scars, peripheral atrophic scars, and choroidal neovascularization (CNV).[2] This disease is rarely reported in Taiwan. We report a case with chorioretinopathy resembling POHS and the clinical course of successful treatment with intravitreal bevacizumab.

2. Case report

A 42-year-old woman came to our clinic because of blurred vision of her right eye for two weeks in June 2011. She had history of hepatitis B and surgery for appendectomy. She denied any systemic symptoms such as general weakness, fever, or jaundice. Her profession was in accounting and her workplace was in the vicinity of a chicken farm. She had travelled overseas, including China, Thailand, and Japan. Her refraction was OD −6.0c−0.5 × 50 and OS −7.0c−0.25 × 60. Her best corrected visual acuity (BCVA) was 20/40 OD and 20/20 OS. The anterior segment was normal in both eyes. Fundus examination of right eye revealed multiple juxtapa-pillary and peripheral small, atrophic punched-out chorioretinal scars. The foveal reflex was diminished with the presence of macular hemorrhage. No atrophic scar was observed in left eye. Both eyes showed peripapillary chorioretinal atrophy. No vitreal inflammation was noted in both eyes [Figure 1]A. Neither eye showed lacquer cracks, Fuchs spots, or posterior staphyloma. Fluorescein angiography (FA) showed hyperfluorescence of the punched-out scars after transit phase in right eye. The macular showed hypo-fluorescence blocked by blood and hyperfluorescence due to leakage in the late phase [Figure 1]B. Linear atrophic tracks were noted at the midperipheral retina [Figure 1]C. FA of left eye did not show abnormal hyperfluorescence. Optic coherence tomography (OCT) showed increased macular thickness of 269 μm, distorted foveal depression, and presence of subretinal fluid in right eye [Figure 1]D. OCT of left eye was of normal contour with macular thickness of 234 mm. Laboratory results, including complete blood count, erythrocyte sedimentation rate, hepatic and renal functions, immunoglobulin (Ig) G and IgM for toxoplasma, were within normal limits. Chest radiography did not show any anomaly. Human leukocyte antigen typing showed A11, A33, B40, B44, Cw5, Cw15, Dr10, Dr11, DQ3, and DQ5.
Figure 1: (A) Fundus photography showed multiple juxtapapillary small, atrophic punched-out chorioretinal scars. The foveal reflex was diminished with macular hemorrhage; (B) fluorescein angiography showed hyperfluorescence of the punched-out scars. The macular showed hypofluorescence blocked by blood and hyperfluorescence with late leakage; (C) linear atrophic tracks were noted at mid-peripheral retina; (D) optic coherence tomography showed increased macular thickness and presence of subretinal fluid.

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The clinical picture resembled POHS with CNV. Oral prednisolone of 60 mg daily was given in an attempt to treat the CNV. Her visual acuity did not improve after two weeks of oral steroid treatment. After informed consent of the patient, intravitreal bevacizumab (IVB) treatments were started. Three injections of IVB of 1.25 mg were given with intervals of 6 weeks between each injection. The oral steroid treatment was discontinued 5 weeks later due to symptoms of gastrointestinal discomfort. Her right BCVA started to improve to 20/30 at 4 weeks and returned to 20/20 at 20 weeks after the first dose of IVB. FA showed absence of late phase leakage at 16 weeks [Figure 2]A. OCT showed macular thickness of 238 μm at 20 weeks and 211 μm at 26 weeks [Figure 2]B.
Figure 2: (A) At 5 weeks after start of intravitreal bevacizumab treatment, the absence of late phase leakage demonstrated regression of choroidal neovascularization; (B) at 14 weeks after start of intravitreal bevacizumab treatment, optic coherence tomography shows normal macular thickness; (C) at 1-year of follow-up, fundus photography shows no recurrence of choroidal neovascularization but enlargement of the atrophic scars (arrow).

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At 1-year of follow-up, her right BCVA was 20/20. OCT showed macular thickness of 205 um without any recurrence of subretinal fluid. However, photography of fundus showed enlargement of the atrophic scars [Figure 2]C.

  3. Discussion Top

Histoplasmosis was rare in Taiwan. Literature review revealed that only nine cases of disseminated histoplasmosis were reported up to 2009 in Taiwan.[3],[4],[5],[6],[7],[8],[9],[10] Among these reports, seven cases had history of overseas travels, four cases had human immunodeficiency virus infections and two cases received long-term immu-nosuppressant treatments due to other diseases. The clinical outcomes were unfavorable, with six deaths among nine cases.

POHS was also rarely reported in Taiwan. Lin et al described a suspected POHS case with papillitis in 1985. However, the presence of vitritis made the diagnosis ambiguous.[11] Chung and colleagues[12] reported two cases with multiple choroidal lesions with inflammation of anterior chamber and vitreous in 1989. The authors concluded with the diagnosis of multifocal choroiditis and panuveitis.[12] No other cases of POHS were reported in literature since then.

The diagnosis of POHS depends mainly on clinical triad of peripapillary atrophic chorioretinal scars, peripheral atrophic scars and CNV.[2] The characteristic atrophic “histo” spots are small, round, yellowish-white lesions scattered in the midperipheral retina and posterior fundus. The differential diagnosis includes disease entities that consist of multiple chorioretinal atrophic lesions and CNV. Age-related macular degeneration occurs mainly in people older than 50 years of age and associates frequently with druses or other retinal pigment epithelial (RPE) abnormalities, including geographic atrophy and focal hyperpigmentation, RPE tear, and RPE detachment. Degenerative myopia features high myopic refraction, long axial length, tilted optic nerves, lacquer cracks, and posterior staphyloma formation. Angioid streak features dark-red linear streaks radiating from optic nerve head, mottled retinal pigmentation called “peau d’orange,” and frequent systemic association with pseudoxanthoma elasticum, Paget disease, or some hemo-globinopathies. Best (vitelliform) macular dystrophy may develope CNV in the late stage. However, the characteristical “sunny side-up egg yolk” vitelliform lesion presents the clue to diagnosis.

The differential diagnosis should also include those non-infectious retinal and choroidal inflammatory disorders presenting with focal and diffuse chorioretinal yellow-white lesions. The term “white dot syndrome” is used to describe these diseases entities.[13] Acute posterior multifocal placoid pigment epitheliop-athy (APMPPE) presents as an acute-onset bilateral chorioretinal inflammation, with viral prodrome in about one-third of cases. Serpiginous choroidopathy is a chronic and recurrent chorioretinal inflammation with serpiginous or geographic pattern of scars in the posterior fundus. Multiple evanescent white syndrome is a self-limiting unilateral disease with multiple gray-white dots and foveal granular orange appearance, which usually improve after 2–6 weeks. Birdshot retinochoroidopathy is a bilateral chronic/ recurrent disease with vitritis, disc edema, vascular sheathing, and characteristic yellow ovoid “birdshot” chorioretinal lesions radiating outward from the disc. Multifocal choroiditis and panuveitis syndrome is a bilateral chronic/recurrent disease with vitritis, mild iritis, and multiple yellow choroidal lesions that later evolve into the “punch-out” lesions similar to POHS. Punctate inner choroid-opathy (PIC) is a bilateral disease, which affects mostly young myopic women, with multiple small well-defined inflammatory chorioretinopathy. Typical PIC lesions are small and more confined to within the arcades. Atypical PIC lesions are larger and may distribute peripapillary and beyond arcades. The active lesions in PIC demonstrate active inflammation, in contrast to the lesions in POHS which present punched-out and focal defect in Bruch’s membrane.[14],[15] Acute zonal occult outer retinopathy (AZOOR) is a rare presumed inflammatory disorder of outer retina with acute loss of one or more zones of visual field. The fundus of AZOOR appears normal initially and later evolves to the appearance resembling retinitis pigmentosa.

The differential diagnosis also includes noninfectious systemic inflammations involving posterior segment of globe. Vogt-Koyanagi-Harada syndrome is a chronic bilateral diffuse granulo-matous panuveitis with accompanying neurologic, auditory, dermatologic involvements. Behcet disease is a chronic occlusive systemic vasculitis with relapsing uveitis, oral ulcer, genital ulcer, and other skin manifestations.

Certain infectious chorioretinopathy may also be considered in the differential diagnosis of this case. Toxoplasmosis is a common cause of infectious chorioretinitis presenting a focal, white retinitis and overlying vitritis (“headlight in the fog”) in its inflammatory stage, and punch-out macular scars in its late stage. Toxocariasis features chronic uveitis and characteristic peripheral granuloma. Systemic infection with ocular involvement, including rubella, and syphilis present pigmentary change in the appearance of “salt-and-pepper.”

Our case was a 42-year-old healthy myopic woman. She was immunocompetent. She had history of overseas travels but never been to the United States. Her history of contact with chicken might be the route of exposure to the fungus. She had the typical clinical triad of peripapillary atrophic chorioretinal scars, peripheral atro-phic scars and CNV. However, lack of histoplasmin test result and non-endemic residence make the diagnosis of POHS less substantial. The lack of lacquer cracks and posterior staphyloma also makes degenerative myopia less likely the cause of CNV. However, the possibility of PIC cannot be totally excluded since atypical cases of PIC may have larger lesions distributed both within and outside the arcades.[15]

CNV is the primary cause of visual loss in POHS and similar disease entities. Many treatment options focused on CNV are reported in literatures. The Macular Photocoagulation Study first documented the effectiveness of focal laser photocoagulation for extrafoveal and juxtafoveal CNV of POHS.[16] For subfoveal CNV, the Verteporfin in Ocular Histoplasmosis study proved photodynamic therapy is better than natural cause ofPOHS.[17],[18] Surgical removal of subfoveal neovascularization was attempted. However, the result of Submacular Surgery Trials showed limited benefits of vitrectomy with extraction of subfoveal membrane in POHS.[19] Corticosteroid, by oral or intravitreal route, was reported to have a stablizing role of CNV through its antiangiogenic effect in some case series. Further studies are warranted to evaluate the effect of corticosteroid treatment.[20],[21]

Antivascular endothelial growth factors, such as bevacizumab, were proved to be effective in CNV in age-related macular degeneration. The results encourage the applications of anti-vascular endothelial growth factor for CNV of other origins. Schadlu and colleagues[22] reported IVB stabilize or improve vision of 85% of treated eyes. Mansour and others[23] demonstrated the effectiveness of IVB with his investigation that 30.9% had at least a three-line gain in vision at 3 months of follow-up. Cionni and coauthors[24] analyzed the long-term outcome and showed that 38% of eyes gained three-line or more and 81.2% of participants maintained or improved at 1 year of follow-up.

Taiwan is not an endemic area for histoplasmosis. Clinicians should be cautious in differential diagnosis of the clinical presentation of POHS or similar disease entities. Early identification and timely treatment with IVB may rescue the patient from preventable vision loss.

  References Top

Ganley JP. Epidemiologic characteristics of presumed ocular histoplasmosis. Acta Ophthalmol Suppl 1973;119:1–63.  Back to cited text no. 1
Meredith TA, Green WR, Key SN, Dolin GS, Maumenee AE. Ocular histoplasmosis: clinicopathologic correlation of 3 cases. Surv Ophthalmol 1977;22:189–205.  Back to cited text no. 2
Lee CH, Chen L, Huang MJ. Disseminated histoplasmosis. Chang Gung Medical J 1977; 1 :14–8.  Back to cited text no. 3
Kao TW, Hung CC, Hsueh PR, Lin TY, Chen MY, Luh KT, et al. Microbiologic and histologic diagnosis of histoplasmosis in Taiwan. J Formos Med Assoc 1997;96:374–8.  Back to cited text no. 4
Hung CC, Wong JM, Hsueh PR, Hsieh SM, Chen MY. Intestinal obstruction and peritonitis resulting from gastrointestinal histoplasmosis in an AIDS patient. J Formos Med Assoc 1998;97:577–80.  Back to cited text no. 5
Liu JW, Huang TC, Lu YC, Liu HT, Li CC, Wu JJ. Acute disseminated histoplas-mosis complicated with hypercalcaemia. JInfect 1999;39:88–90.  Back to cited text no. 6
Lian WB, Lee YT, Lee CM. Disseminated histoplasmosis in AIDS: a case report. J Intern Med Taiwan 2000;11:132–8.  Back to cited text no. 7
Hung MN, Sun HY, Hsueh PR, Hung CC, Chang SC. Meningitis due to histoplasma capsulatum and Mycobacterium tuberculosis in a returned traveler with acquired immunodeficiency syndrome. J Formos Med Assoc 2005;104:860–3.  Back to cited text no. 8
Lai CH, Huang CK, Chin C, Yang YT, Lin HF, Lin HH. Indigenous case of disseminated histoplasmosis, Taiwan. EmergInfect Dis 2007;13:127–9.  Back to cited text no. 9
Fu PK, Hsu JY, Chin CS. Disseminated histoplasmosis after corticosteroid treatment for hemolytic anemia. Thorac Med 2009;24:260–5.  Back to cited text no. 10
Lin CL, Yen MY, Chu YH. Presumed ocular histoplasmosis with papillitis. Acta Soc Ophthalmol Sinicae 1985;24:456–60.  Back to cited text no. 11
Chung YM, Yang CS, Chen JF. Multifocal choroiditis and panuveitis. Acta Soc Ophthalmol Sinicae 1989;28:849–55.  Back to cited text no. 12
Quillen DA, Davis JB, Gottlieb JL, Blodi BA, Callanan DG, Chang TS, et al. The white dot syndrome. Am JOphthalmol 2004;137:538–50.  Back to cited text no. 13
Amer R, Lois N. Punctate inner choroidopathy. Surv Ophthalmol 2011;56: 36–53.  Back to cited text no. 14
Essex RW, Wong J, Fraser-Bell S, Sandbach J, Tufail A, Bird AC, et al. Punctate inner choroidopathy: clinical features and outcomes. Arch Ophthalmol 2010;128:982–7.  Back to cited text no. 15
Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis: results of a randomized clinical trial. Arch Ophthalmol 1987;105:1499–507.  Back to cited text no. 16
Verteporfin in Ocular Histoplasmosis (VOH) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: one-year results of an uncontrolled, prospective case series. Ophthalmology 2002;109:1499–505.  Back to cited text no. 17
Verteporfin in Ocular Histoplasmosis Study Group. Photodynamic therapy with verteporfin in ocular histoplasmosis: uncontrolled, open-label two-year study. Ophthalmology 2004;111:1725–33.  Back to cited text no. 18
Submacular Surgery Trials Research Group. Surgical removal vs observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic: I. Ophthalmic findings from a randomized clinical trial: Submacular Surgery Trials (SST) Group H Trial: SST Report No. 9. Arch Ophthalmol 2004;122:1597–611.  Back to cited text no. 19
Rechtman E, Allen VD, Danis RP, Pratt LM, Harris A, Speicher MA. Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome. Am J Ophthalmol 2003;136:739–41.  Back to cited text no. 20
Martidis A, Miller DG, Ciulla TA, Danis RP, Moorthy RS. Corticosteroids as an antiangiogenic agent for histoplasmosis-related subfoveal choroidal neo-vascularization. J Ocul Pharmacol Ther 1999;15:425–8.  Back to cited text no. 21
Schadlu R, Blinder KJ, Shah GK, Holekamp NM, Thomas MA, Grand MG, et al. Intravitreal bevacizumab for choroidal neovascularization in ocular histoplas-mosis. Am J Ophthalmol 2008;145:875–8.  Back to cited text no. 22
Mansour AM, Mackensen F, Arevalo JF, Ziemssen F, Mahendradas P, Mehio-Sibai A, et al. Intravitreal bevacizumab in inflammatory ocular neovascularization. Am J Ophthalmol 2008;146:410–6.  Back to cited text no. 23
Cionni DA, Lewis SA, Petersen MR, Foster RE, Riemann CD, Sisk RA, et al. Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal neovascularization secondary to ocular histoplasmosis. Ophthalmology 2011;119:327–32.  Back to cited text no. 24


  [Figure 1], [Figure 2]

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